Analysis of 17 randomized controlled trials involving 14,645 subjects indicates that tirzepatide has similar pancreatitis risks compared to placebo.
Tirzepatide did not show an increased risk of pancreatitis compared to placebo or other treatments like insulin and GLP-1 receptor agonists.
All doses of tirzepatide led to greater increases in pancreatic amylase and lipase levels than placebo and insulin.
Tirzepatide 10 and 15 mg resulted in greater reductions in fasting insulin levels compared to placebo.
Tirzepatide produced larger percent reductions in fasting insulin, C-peptide, and glucagon levels than GLP-1 receptor agonists.
Percent reductions in insulin resistance () were greater with all doses of tirzepatide compared to placebo and GLP-1 receptor agonists.
Simplified
BACKGROUND: Endogenous glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP) regulate islet cell function. GLP-1 receptor agonists (GLP-1RAs) have been associated with an elevated risk of acute pancreatitis. Data on the pancreatic safety of tirzepatide (a dual GLP-1 and GIP agonist) and its effects on islet cell function in randomized controlled trials (RCTs) are scarce. Moreover, no meta-analysis has comprehensively examined such effects of tirzepatide.
METHODS: Electronic databases were searched for RCTs with tirzepatide as the intervention and a placebo or active comparator as the control. The primary outcome was adjudication-confirmed pancreatitis; secondary outcomes were the percent changes from baseline in serum pancreatic amylase, lipase, insulin, C-peptide, glucagon, and homeostasis model assessment of insulin resistance ().
RESULTS: Seventeen RCTs with 18 published reports involving 14,645 subjects were analyzed. Over a follow-up duration of 12-72 weeks, tirzepatide had identical risks of pancreatitis to placebo (tirzepatide 5 mg: RR 2.04, 95% CI [0.27-15.69], = 0.49; 10 mg: RR 0.63, 95% CI [0.08-5.12], = 0.67; and 15 mg: RR 1.26, 95% CI [0.36-4.98], = 0.72). Tirzepatide was also associated with comparable risks of pancreatitis to insulin and GLP-1RAs. However, tirzepatide (at all doses) caused greater increases in pancreatic amylase and lipase than placebo and insulin. Individuals on tirzepatide 15 mg and GLP-1RAs had similar risks of having increased lipase levels. The percent reductions in fasting insulin were greater with tirzepatide 10 and 15 mg than with placebo. All doses of tirzepatide caused greater percent reductions in fasting insulin, C-peptide, and glucagon than GLP-1RAs. Compared to placebo and GLP-1RAs, the percent reductions in HOMA2-IR were greater with all doses of tirzepatide. p p p
CONCLUSION: The meta-analysis provides evidence of the safety of tirzepatide regarding pancreatitis and establishes its positive effect on islet cell functions and insulin resistance.
Key numbers
2.04
for (5 mg)
Risk of for 5 mg vs. placebo.
-37.0%
Percent Change in (15 mg)
Percent reduction in with 15 mg vs. placebo.
25.46%
Percent Change in (5 mg)
Percent increase in for 5 mg vs. placebo.
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